TWEAK receptor (TweakR), also known as Fn14 or TNFRSF12A, is a member of the tumor necrosis factor receptor superfamily. It is expressed on the surface of cancer cells derived from a variety of solid tumors. Expression of TweakR can be detected on some normal tissues, including the kidney (Bowman's capsule), liver (hepatocytes), and on proliferating endothelial cells and fibroblasts (Meighan-Mantha, et al., 1999, J. Biol. Chem. 1999; 274:33166-33176; and Jakubowski, et al., 2002, J. Cell Sci. 2002; 115:267-274). Expression of TweakR is up-regulated by growth factors in vitro and in vivo in response to tissue injury, regeneration, and inflammation (Feng, et al., 2000, Am. J. Pathol., 156:1253-1261; Wiley, et al., 2001, Immunity, 15:837-846; and Desplat-Jego, et al., 2005, J. Neuroimm., 133:116-123).
DNA and amino acid sequences corresponding to the TweakR have been reported (see, e.g., U.S. Pat. No. 6,531,447, U.S. Pat. No. 6,824,773, U.S. Patent Application Publication No. 2006/0025574, PCT Publication No. WO 98/55508, PCT Publication No. WO 99/61471). Similarly, methods of making and using TweakR antagonists and agonists to modulate angiogenesis associated with immunological disorders and cancer have been reported (see, e.g., U.S. Pat. No. 6,727,225, U.S. Pat. No. 6,824,773, U.S. Pat. No. 7,001,992, U.S. Pat. No. 7,169,387, U.S. Pat. No. 7,208,151, U.S. Patent Application Publication No. 2005/0054047, U.S. Patent Application Publication No. 2005/0208046, U.S. Patent Application Publication No. 2006/0084143, PCT Publication No. WO 00/42073). However, none of these reports have identified monoclonal antibodies that bind to TweakR and exhibit anti-tumor effects. These deficiencies have been addressed, as described herein, by the identification of antibodies that bind to TweakR and characterization of their biological activities. The identification of anti-TweakR monoclonal antibodies has led to the development of compositions for the treatment of solid tumors, and also provides screening tools for diagnostic use.